University of Connecticut scientists have found that both severe epilepsy and breathing irregularities leading to sudden death are possibly linked to the same gene mutation, Scn1a. 

Previously, it was thought that seizures were travelling through the brain and leading to unexpected death in epilepsy (SUDEP), despite seizures occurring in the brain’s cortex and away from areas controlling life-sustaining processes like breathing. People with SUDEP also die without any obvious seizure, and epilepsy sufferers can have breathing problems without any seizure.

To find the real reason for SUDEP, the researchers raised mice with a mutation for a severe form of epilepsy, Dravet syndrome. This is caused by mutations in the Scn1a gene that shapes the channels through which sodium moves in and out of brain cells. Should sodium channels fail to properly function, cells can get overexcited and cause a seizure.

The Dravet syndrome mutation occurs in gene Scn1a, which is responsible for roughly another 1,200 different epilepsy variants. In Dravet syndrome, the Scn1a mutation makes the sodium channels less active, making cells underactive. It also mostly affects inhibitory cells, which are in charge of calming the brain down.

The researchers tested two things in the mice: whether mice with Dravet syndrome had bad seizures which became more severe when the mice became hot, as is the case with humans; and whether the cells in the mice’s brainstem controlling breathing were normal or changed by the mutation.

It was found that the mice did have heat-exacerbated seizures, like humans; regarding the second question, the Dravet mice had disordered breathing, sometimes hyperventilating for no apparent reason. The mice also had long apneas, and didn’t breathe more in response to high levels of carbon dioxide, as is normally the case.

The researchers then looked at part of the mice’s brainstem which controls breathing, finding that the inhibitory cells were less active than they should have been, leading the excitatory neurons to run wild and tell the part of the brain generating breathing rhythm to push faster.

The scientists have not yet been able to specify what exactly is wrong with the breathing circuit of the mice. Next, they will look at mice which are only expressing the Scn1a mutation in the brainstem or only in the cortex, to see if they have the same problems. If they don’t, it would suggest the hypothesis about seizures descending from the cortex to the brainstem is false.

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